{"doi":"10.3389/fimmu.2022.877682","title":"Efficient derivation of chimeric-antigen receptor-modified TSCM cells","abstract":"Chimeric-antigen receptor (CAR) T-cell immunotherapy employs autologous-T cells modified with an antigen-specific CAR. Current CAR-T manufacturing processes tend to yield products dominated by effector T cells and relatively small proportions of long-lived memory T cells. Those few cells are a so-called stem cell memory T (T SCM ) subset, which express naïve T-cell markers and are capable of self-renewal and oligopotent differentiation into effector phenotypes. Increasing the proportion of this subset may lead to more effective therapies by improving CAR-T persistence; however, there is currently no standardized protocol for the effective generation of CAR-T SCM cells. Here we present a simplified protocol enabling efficient derivation of gene-modified T SCM cells: Stimulation of naïve CD8+ T cells with only soluble anti-CD3 antibody and culture with IL-7 and IL-15 was sufficient for derivation of CD8+ T cells harboring T SCM phenotypes and oligopotent capabilities. These in-vitro expanded T SCM cells were engineered with CARs targeting the HIV-1 envelope protein as well as the CD19 molecule and demonstrated effector activity both in vitro and in a xenograft mouse model. This simple protocol for the derivation of CAR-T SCM cells may facilitate improved adoptive immunotherapy.","journal":"Frontiers in Immunology","year":2022,"id":256610,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":19,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9541,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":905886,"name":"Charles J. Kuhlmann","orcid":"0000-0003-4438-5814","position":1,"is_corresponding":false},{"id":905887,"name":"Joshua Chan","orcid":"0009-0002-4696-4588","position":2,"is_corresponding":false},{"id":906456,"name":"Patrick Y. Kim","orcid":null,"position":3,"is_corresponding":false},{"id":499074,"name":"Irvin S. Y. Chen","orcid":"0000-0003-1199-2415","position":4,"is_corresponding":false},{"id":499073,"name":"Masakazu Kamata","orcid":"0000-0003-0323-3742","position":5,"is_corresponding":false},{"id":500083,"name":"Emiko Kranz","orcid":null,"position":0,"is_corresponding":true}],"reference_count":52,"raw_metadata":null,"created_at":"2026-07-19T00:25:25.728895Z","pmid":"35967430","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}